Cellular Injury in Phosphate Depletion: Pathogenesis and Mechanisms in the Myocardium

  • N. Brautbar
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 194)


Phosphate depletion is commonly associated with proximal muscle weakness, muscle pain, impaired resting membrane potential (1) and mild elevation of creatine phosphokinase and aldolase (1). Phosphorus depletion in experimental animals has been shown to cause severe muscle weakness and creatinuria (2). Fuller and associates (1) examined the effect of phosphate depletion and repletion on skeletal muscle in the dog; they found that resting muscle membrane potential and muscle content of potassium and total phosphorus fell, while muscle sodium, chloride and water content rose with phosphate depletion. All these abnormalities returned to, or towards, normal with phosphate repletion. Further studies by the same group of investigators demonstrated that overt rhabdomyolysis may be precipitated by the superimposition of severe hypophsophatemia on pre-existing subclinical myopathy (3). In addition, a rise in creatine phosphokinase occurs in patients who develop acute fall in the serum levels of phosphorus (4). The observation that myopathie symptoms develop only in severe hypophosphatemia (4), and that acute hypophosphatemia may be associated with acute rhabdomyolysis suggest that both serum and cellular inorganic phosphorus levels play an important role in the myopathy.


Short Chain Fatty Acid Creatine Phosphate Inorganic Phosphorus Creatine Phosphokinase Phosphate Depletion 
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  1. 1.
    T. J. Fuller, N. W. Carter, C. Barcenas, J. P. Knochel, Reversible changes of the muscle cell in experimental phosphorus deficiency.,J Clin Invest 57: 1019 (1976).CrossRefGoogle Scholar
  2. 2.
    H. Schneider, and H. Steenbock, A low phosphate diet and the response of rats to vitamin D. J Biol Chem 128:159 (1939) Google Scholar
  3. 3.
    J.P.Knochel,C.Barcenas,J.R.Cotton, Hypophosphatemia and rhabdomyolysis. J Clin Invest62:1240(1978).CrossRefGoogle Scholar
  4. 4.
    J. P. Knochel, Hypophosphatemia. West.J Med.134: 15 (1981).Google Scholar
  5. 5.
    S. Bessman, P. Gegan, Transport of energy in muscle: the phosphoryl creatine shuttle. Science 211: 448 (1981).Google Scholar
  6. 6.
    M. Mahler, Progressive loss of mitochondrial creatine phosphokinase activity in muscular dystrophy.Biochem Bioahvs Res Comm.88: 895–906 (1979).CrossRefGoogle Scholar
  7. 7.
    V.Saks,N.Lipin,V.Sharnov,E.Chagov,The localization of the MM isoenzyme of creatine kinase on the surface membrane of myocardial cells and its functional coupling to ouabain inhibited(Na,K)ATPase.Biochim Biochvs ACTA 465: 550 (1970).CrossRefGoogle Scholar
  8. 8.
    S.Bessman,P.Gegen,W.Yeng,W.,and S.Viitanen,Intimate coupling of creatine phosphokinase and myofibrillar adenosinetriphosphataseBiochem Bionhvs Res Comm.96: 1414 (1980).Google Scholar
  9. 9.
    N. Brautbar, R. Baczynski, C. Carpenter, S. Moser, P. Geiger, P. Finander and S. G. Massry, Impaired energy metabolism in rat myocardium during phosphate depletion. Am J. Physiol. 242: F669–704 (1982).Google Scholar
  10. 10.
    N.Brautbar,C.Carpenter,R.Baczynski,R.Kohen,and S.G.Massry,Impaired energy metabolism in skeletal muscle during phosphate depletion.Kid Intern.24:53–57(1983).Google Scholar
  11. 11.
    N.Brautbar,J.Tabernero-Romo,J.Coats,S.Massry,Effects of phosphate depletion on lipid metabolism.Kid.Int.(in press).Google Scholar
  12. 12.
    R.A.DeFronzo,and R. Lang, Hypophosphatemia and glucose intolerance: Evidence for tissue insensitivity to insulin.New Engl.J Med.303: 1259–1263 (1980).CrossRefGoogle Scholar
  13. 13.
    J.L.Davis,S.B.Lewis,T.A.Schultz,R.A.Kaplan,and J.D.Wallin,Acute and chronic phosphate depletion as a modulator of glucose uptake in rat skeletal muscle.Life Science24:629–632(1979).CrossRefGoogle Scholar
  14. 14.
    W. H. Horl, W. Kreusser, A. Heidland, and E. Ritz, Abnormalities of glycogen metabolism in cardiomyopathy of phosphorus depletion,in:Phosphate and Mineralis in Health and Disease. Editors, S.G. Massry, E. Ritz and H. Jahn, pp 343–350, Plenum Press, New York, (1980).Google Scholar
  15. 15.
    C. L. Hoppel, Carnitine palmitoyl transferase and transport of fatty acids, in:The Enzymes of Biological Membranes. Vol. 2. Editors: A. Martonosi, Plenum Press, New York, pp 119–143,(1976).Google Scholar
  16. 16.
    E. P. Brass, and C. L. Hoppel, Carnitine metabolism in the fasting rat. J Biol Chem 253: 2688–2693 (1978).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • N. Brautbar
    • 1
  1. 1.Department of Medicine and Department of Pharmacology and NutritionUniversity of Southern California School of MedicineLos AngelesUSA

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